OP0177 IMMUNOGENICITY INDUCED BY TWO AND THREE DOSES OF THE BNT162B2 mRNA VACCINE IN PATIENTS WITH AUTOIMMUNE INFLAMMATORY RHEUMATIC DISEASES AND IMMUNOCOMPETENT CONTROLS: A LONGITUDINAL MULTI-CENTER STUDY
Authors: V. Furer, T. Eviatar, H. Peleg, D. Hagin, T. Freund, D. Levartovsky, D. Paran, I. Kaufman, A. Broyde, A. Polachek, O. Elalouf, J. Feld, A. Haddad, T. Gazitt, M. Elias, N. Hijaze, F. Kharouf, S. Gertel, S. Nevo, S. Pel, D. Zisman, O. Elkayam
Journal: Annals of the Rheumatic Diseases (2022)

Background Data on the kinetics of the immune response to SARS-CoV-2 vaccination in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited. Objectives To evaluate the kinetics of the immune response induced by two and three doses of the BNT162b2 mRNA vaccine in adult patients with AIIRD and immunocompetent controls. Methods A prospective multicenter study investigated the antibody response to the BNT162b2 vaccine by serial measurement of serum anti-SARS-CoV-2 S1/S2 IgG titers at the following time points: 2-6 weeks (AIIRD n=720, controls n=122) and six months (AIIRD n=628, controls=116) after the second vaccine dose, and 2-6 weeks after the third vaccine dose (AIIRD n=169, controls n=45). A seropositive response was defined as a detectable anti-S1/S2 IgG titer ≥ 15 BAU/ml. T-cell immune response was evaluated in a sample of patients (n=28) and controls (n=9) by intracellular staining of S-stimulated CD4 + T-cells for TNFα and IFNγ production. Results The two-dose vaccine regimen induced a higher humoral response in controls compared to patients, as reflected by the post-vaccination seropositivity rates of 100% vs 84.72%, p&lt;0.0001, and 96.55% vs 74.26%, p&lt;0.0001 at 2-to-6 weeks and at 6 months, respectively. The decline of S1/S2 IgG titers within six months was similar in controls and patients. Following the 3 rd vaccine, the seropositivity rate increased to 80.47% and 100% in AIIRD and control groups, p=0.0028, with a significantly higher increase of S1/S2 IgG titers in controls compared with AIIRD patients, 284.09±76.58 vs 219.39±151.55 BAU/ml, p=0.0016. At all-time points, S1/S2 IgG titers were significantly lower in AIIRD patients compared with controls (Figure 1). We further investigated the impact of therapies on the vaccine‘s immunogenicity (Figure 1). Glucocorticoids (GC) were associated with a significantly lower seropositivity rate and lower S1/S2 IgG titers compared to controls at all time points. Monotherapy with methotrexate (MTX) was associated with a comparable to controls humoral response at all time points. Anti-cytokine biologics (TNFi, IL6i, IL17i) were associated with an initial high seropositivity rate, similar to controls, followed by a steeper decline at 6 months, 79.82% vs 96.55%, p=0.0001, and restoration of seropositivity after the 3 rd vaccine dose in all patients. JAKi were associated with a mildly decreased seropositivity rate after the 2 nd vaccine dose and similar to controls response after the 3 rd vaccine dose. Abatacept was associated with a reduced immunogenicity after the 2 nd vaccine dose, but was restored to 100% seropositivity after the 3 rd vaccine dose. Rituximab (RTX) significantly blunted the humoral response at all time points, with a seropositivity rate of 42% after the 2 nd vaccine dose, 29% at 6 months, and with increase to 40% after the 3 rd vaccine dose. A third of the RTX-treated patients who were seronegative after two vaccine doses, seroconverted after the 3 rd dose. The multivariate model for predicting the seropositive response to vaccination found that higher S1/S2 IgG titers after the 2 nd vaccine dose was associated with a higher seropositivity rate following the 3 rd vaccine dose, OR 1.026 (1.008-1.045), p=0.0027, and that treatment with RTX was associated with a 14.3-fold risk for a negative humoral response, p≤0.0001. Cellular immune response, evaluated mainly in RTX treated patients, was preserved prior to and after the 3 rd vaccine dose and was similar to controls. Conclusion Over a six-month period, the two dose BNTb262 vaccination was associated with a similar extent of waning of the humoral immune response in AIIRD patients and controls. The 3 rd vaccine dose restored the response in all controls and in patients treated with MTX monotherapy, anti-cytokine biologics, abatacept, and JAKi. Treatment with GC and RTX was associated with an impaired humoral response at all time points. Acknowledgements We would like to thank the statistician Mr Yishai Friedlander and Mr Yoram Neufeld for their valuable assistance. Disclosure of Interests None declared